CDK4/6 Inhibitor Treatments in Patients with Hormone Receptor Positive, Her2 Negative Advanced Breast Cancer: Potential Molecular Mechanisms, Clinical Implications and Future Perspectives

Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer is the most common breast cancer subtype, and endocrine therapy (ET) remains its therapeutic backbone. Although anti-estrogen therapies are usually effective initially, approximately 50% of HR+ pat...

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Bibliographic Details
Published in:Cancers 2021-01, Vol.13 (2), p.332
Main Authors: Roberto, Michela, Astone, Antonio, Botticelli, Andrea, Carbognin, Luisa, Cassano, Alessandra, D'Auria, Giuliana, Fabbri, Agnese, Fabi, Alessandra, Gamucci, Teresa, Krasniqi, Eriseld, Minelli, Mauro, Orlandi, Armando, Pantano, Francesco, Paris, Ida, Pizzuti, Laura, Portarena, Ilaria, Salesi, Nello, Scagnoli, Simone, Scavina, Paola, Tonini, Giuseppe, Vici, Patrizia, Marchetti, Paolo
Format: Article
Language:English
Subjects:
Antiestrogens
Breast cancer
Cancer therapies
Cell growth
Chemotherapy
Cyclin-dependent kinase 4
Cyclin-dependent kinases
Drug development
Endocrine therapy
Epidermal growth factor
ErbB-2 protein
Estrogens
Gene expression
Kinases
Ligands
Metastasis
Molecular modelling
Mutation
Ovaries
Proteins
Quality of life
Review
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Summary:Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer is the most common breast cancer subtype, and endocrine therapy (ET) remains its therapeutic backbone. Although anti-estrogen therapies are usually effective initially, approximately 50% of HR+ patients develop resistance to ET within their lifetime, ultimately leading to disease recurrence and limited clinical benefit. The recent addition of cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (palbociclib, ribociclib, abemaciclib) to ET have remarkably improved the outcome of patients with HR+ advanced breast cancer (ABC) compared with anti-estrogens alone, by targeting the cell-cycle machinery and overcoming some aspects of endocrine resistance. However, which patients are the better candidates for these drugs, which are the main characteristics for a better selection of patients or if there are predictive biomarkers of response, is still unknown. In this review we reported the mechanism of action of CDK4/6 inhibitors as well as their potential mechanism of resistance, their implications in clinical practice and the forthcoming strategies to enhance their efficacy in improving survival and quality of life of patients affected with HR+, HER2-, ABC.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13020332